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71.
Biotransformation of 4‐fluoro‐N‐(1‐{2‐[(propan‐2‐yl)phenoxy]ethyl}‐8‐azabicyclo[3.2.1]octan‐3‐yl)‐benzenesulfonamide,a novel potent 5‐HT7 receptor antagonist with antidepressant‐like and anxiolytic properties: In vitro and in silico approach
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Karolina Słoczyńska Katarzyna Wójcik‐Pszczoła Vittorio Canale Paweł Żmudzki Paweł Zajdel Elżbieta Pękala 《Journal of biochemical and molecular toxicology》2018,32(5)
The aim of the study was to investigate the metabolism of 4‐fluoro‐N‐(1‐{2‐[(propan‐2‐yl)phenoxy]ethyl}‐8‐azabicyclo[3.2.1]octan‐3‐yl)‐benzenesulfonamide (PZ‐1150), a novel 5‐HT7 receptor antagonist with antidepressant‐like and anxiolytic properties, by the following three ways: in vitro with microsomes; in vitro employing Cunninghamella echinulata, and in silico using MetaSite. Biotransformation of PZ‐1150 with microsomes resulted in five metabolites, while transformation with C. echinulata afforded two metabolites. In both models, the predominant metabolite occurred due to hydroxylation of benzene ring. In silico data coincide with in vitro experiments, as three MetaSite metabolites matched compounds identified in microsomal samples. In human liver microsomes PZ‐1150 exhibited in vitro half‐life of 64 min, with microsomal intrinsic clearance of 54.1 μL/min/mg and intrinsic clearance of 48.7 mL/min/kg. Therefore, PZ‐1150 is predicted to be a high‐clearance agent. The study demonstrated the applicability of using microsomal model coupled with microbial model to elucidate the metabolic pathways of compounds and comparison with in silico metabolite predictions. 相似文献
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The diploid Mexican species S. bulbocastanum (blb) was used as a source of late blight resistance in somatic hybridization with the potato (S. tuberosum, tbr) dihaploid H-8105. The produced 2x blb (+) 2x tbr H-8105 somatic hybrids did not retain the blb parent's characteristic high resistance to P. infestans. The revealed aneuploidy of blb (+) tbr H-8105 hybrids indicated a possible loss of individual blb chromosome(s) carrying the resistance genes. Four hybrid clones differing in terms of their ploidy, morphology and growth potential were analysed for the presence of all twelve blb chromosomes (linkage groups). The RAPD markers assigned to particular chromosomes were selected on the basis of the linkage map of S. bulbocastanum constructed by Naess et al., Mol. Gen. Genom. 265 (2001) 694-704. Of the 86 markers analysed, twelve (14%) were common for blb and H-8105, while 34 (40%) and 40 (46%) markers were specific for the blb and H-8105 genome, respectively; this confirms the differences between the nuclear genomes of the two species. Seventeen markers (20%) present in one or the other parent were absent in the hybrids, and only one new marker was found in the hybrids. The poorly growing, aneuploid and chimeric hybrids had the same band profiles as the well growing, morphologically normal hybrids, except for two bands that were present only in normal hybrids. The presence of eleven blb linkage groups in the blb (+) tbr H-8105 hybrids was confirmed. The markers specific for the second linkage group (chromosome 2) of blb were not present in the RAPD patterns of the somatic hybrids analysed, suggesting a loss or rearrangement of this chromosome in the combined nuclear genome of the hybrids. 相似文献
74.
A study of the species composition of mayfly communities in connection with environmental parameters was made in headwater streams of the Pieniny Mts. The rhithral zone is inhabited maximally by 19 mayfly species. In most of the streams studied the mayfly communities were found to be similar, however the vertical zonation which reflected human impact was visible (NMDS analysis). The main factors responsible for mayfly communities at all the sites studied were stream regulation and organic pollution, followed by type of bottom substrate (pebble and gravel), riparian vegetation (shrubs), pH and water temperature. At undisturbed sites the most important factors were pH, substrate type, distance from the source, current velocity and riparian vegetation (CCA analysis). Analysis of mayfly communities and environmental characteristics in different seasons showed that occurrence of mayfly species varied substantially depending on the season. Only in early spring and autumn do mayfly communities occur which are dependent on many environmental factors, the most significant of which are substrate type, phosphate, distance from source and altitude (CCA analysis). 相似文献
75.
Marian L. Kruzel Jeffrey K. Actor Michał Zimecki Jasen Wise Paulina Płoszaj Shaper Mirza Mark Kruzel Shen-An Hwang Xueqing Ba Istvan Boldogh 《Journal of biotechnology》2013
Lactoferrin, an iron-binding protein found in high concentrations in mammalian exocrine secretions, is an important component of the host defense system. It is also a major protein of the secondary granules of neutrophils from which is released upon activation. Due to its potential clinical utility, recombinant human lactoferrin (rhLF) has been produced in various eukaryotic expression systems; however, none of these are fully compatible with humans. Most of the biopharmaceuticals approved by the FDA for use in humans are produced in mammalian expression systems. The Chinese hamster ovary cells (CHO) have become the system of choice for proteins that require post-translational modifications, such as glycoproteins. 相似文献
76.
Szoszkiewicz Krzysztof Jusik Szymon Lewin Iga Czerniawska-Kusza Izabela Kupiec Jerzy Mirosław Szostak Marta 《Hydrobiologia》2018,808(1):327-342
Hydrobiologia - The aim of the study was to compare the patterns of development of macrophytes and macroinvertebrates in different types of reference mountain rivers. The study is based on... 相似文献
77.
Nitrifying granules cultivation in a sequencing batch reactor at a low organics-to-total nitrogen ratio in wastewater 总被引:4,自引:0,他引:4
It is possible to cultivate aerobic granular sludge at a low organic loading rate and organics-to-total nitrogen (COD/N) ratio
in wastewater in the reactor with typical geometry (height/diameter = 2.1, superficial air velocity = 6 mm/s). The noted nitrification
efficiency was very high (99%). At the highest applied ammonia load (0.3 ± 0.002 mg NH4+–N g total suspended solids (TSS)−1 day−1, COD/N = 1), the dominating oxidized form of nitrogen was nitrite. Despite a constant aeration in the reactor, denitrification
occurred in the structure of granules. Applied molecular techniques allowed the changes in the ammonia-oxidizing bacteria
(AOB) community in granular sludge to be tracked. The major factor influencing AOB number and species composition was ammonia
load. At the ammonia load of 0.3 ± 0.002 mg NH4+–N g TSS−1 day−1, a highly diverse AOB community covering bacteria belonging to both the Nitrosospira and Nitrosomonas genera accounted for ca. 40% of the total bacteria in the biomass. 相似文献
78.
In recent years, Enterococcus faecalis has emerged as an important opportunistic nosocomial pathogen capable of causing dangerous infections. Therefore, there is an urgent need to develop novel antibacterial agents to control this pathogen. Bacteriophages have very effective bactericidal activity and several advantages over other antimicrobial agents and so far, no serious or irreversible side effects of phage therapy have been described. The objective of this study was to characterize a novel virulent bacteriophage φ4D isolated from sewage. Electron microscopy revealed its resemblance to Myoviridae, with an isometric head (74 ± 4 nm) and a long contractile tail (164 ± 4 nm). The φ4D phage genome was tested using pulsed-field gel electrophoresis and estimated to be 145 ± 2 kb. It exhibited short latent period (25 min) and a relatively small burst size (36 PFU/cell). Tests were conducted on the host range, multiplicities of infection (MOI), thermal stability, digestion of DNA by restriction enzymes, and proteomic analyses of this phage. The isolated phage was capable of infecting a wide spectrum of enterococcal strains. The results of these investigations indicate that φ4D is similar to other Myoviridae bacteriophages (for example φEF24C), which have been successfully used in phagotherapy. 相似文献
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